The present invention relates to dramatization, and, more particularly relates to a process for reacting a water soluble polymer with a water insoluble derivation agent and product by same.
Terms such as suspension polymerization and interracial polymerization are known to be used to describe processes by which polymers are synthesized by cross-linking of their mongers utilizing a polymerizing agent. Polymerization is known to occur within such processes heterogeneously, where the mongers, which are usually water insoluble, form tiny droplets which act as a reservoir of react ants. In some instances, surfactants may be added to facilitate droplet formation and stabilization.
The polymerization initiator or polymerizing agent may be either water soluble or water insoluble. In the case where the polymerization initiator is water-insoluble, polymerization occurs within the monomer droplet to form latex""s (suspension polymerization). When water soluble polymerization initiators are employed, polymerization occurs within micelles formed from the added surfactants (emulsion polymerization). Interracial polymerization describes a process whereby polymers are formed at the interface of two immiscible liquids, each containing a reacting monomer in solution. Each of the mentioned processes, suspension, emulsion and interracial polymerization, are polymerization processes wherein the polymer is prepared at the interface of immiscible liquids.
Dramatization is a term used to describe a process whereby functional groups pendant to a polymer chain are chemically modified or reacted in some way to change some character of the polymer. Typically, this is facilitated in solvents which are capable of dissolving the polymer and the derivation agent. Solvents are necessary because such reactions do not occur unless the reacting species (i.e., the polymer and derivation agent) can be brought into intimate contact. For that matter, a common or miscible solvent is almost always used in prior art polymer dramatization processes. Alternatively, phase transfer catalysts may be utilized to react polymers and derivation agents in certain instances, but the phase transfer catalysts are costly and of limited general utility.
Those skilled in the art are continuously looking to uncover or create new polymers, particularly in the fields of biochemistry. For that matter, great interest has recently been shown in a biopolymer known as hyaluronic acid (HA) for its usefulness in a variety of personal and health care products. Hyaluronic acid is a member of a broad class of naturally occurring polyanionic carbohydrates collectively known as glycosaminoglycans (GAGs). Hyaluronic acid consists of repeating units of the of N-acetyl-D-glucosamine and D-glucuronic acid (its primary structure), joined by a xcex21-4 glucosaminic bond (FIG. 1). The molecular weight reported for hyaluronic acid varies between 50,000 to 80,000,000 Daltons depending on the source, method of isolating and method of size determination.
Hyaluronic acid is also a biomolecule which is naturally present in connective tissue, synovial fluid, adult human skin, etc., HA functions as a biomolecule to impart structure and rigidity to the tissue or biomaterials within which it is present. Accordingly, HA is biocompatible such that HA and HA derivatives introduced systemically are normally well accepted by the human body. Hyaluronic acid is also believed to regulate cell morphology and to protect organisms from bacterial and/or other external factors. This protective action is believed related to HA""s high viscosity and water solubility. HA""s high viscosity is attributed to the extensive hydrogen bonded network present in its carboxylate form, which also facilitates the formation of highly viscous HA gels, or hydrogels.
Many novel HA-based products are known and available in the marketplace which utilize HA""s unique biocompatibility. For example, Biocare Polymer HA-24, Biocare AS, Visible Youth, Hylaform, Healon, Synvisc, Seprfilm, and Sepragel, are merely several known HA-containing products available in the US and world markets. Such products have a broad range of applications such as opthalmics, wound repair, surgical aids, cosmetic moisturizers, etc., as well as the development of bioerodable scaffolding for tissue engineering, and regeneration.
HA, therefore, is an extremely important molecule (i.e., biopolymer), applications for which may be improved by its dramatization. For example, attachment to HA of a compatible molecule could further enhance the biofunction facilitated by the HA-based product, or provide for a function in addition to that provided by the HA. Hence, it would be desirable to develop a process for derivation polymeric moieties, such as HA, in a safe and efficacious manner to realize desired polymeric entities with improved functional properties.
In this invention, we describe a process whereby polymers present within a solution may be derivative by a derivation agent therein which is ordinarily insoluble in the solvent. Preferably, the solvent is water and the polymer is water soluble. The water and the water soluble polymer are mixed with the water-insoluble derivation agent, and the mixture is emulsified using a Polytron(trademark) homogenizer. The homogenizer action renders the water insoluble derivation agent within the mixture into the form of tiny droplets, typically less than 1 micron in diameter. To facilitate emulsification, the derivation agent is preferably a liquid, or, in some instances, a highly concentrated solution in a suitable water-insoluble solvent. The polymer is compelled to undergo dramatization at the interface between the aqueous phase and the emulsified derivation agent. Hence, the process is referred to as interracial dramatization.
The process of the present invention is useful for several reasons. First, by utilizing the process described herein, it is possible to react a polymer with an agent where the react ants normally do not react because their wide differences in solubilities prevent the intimate contact necessary for reaction. The second reason is that the process is an alternative process to the more costly emulsion polymerization processes known in the art. The (cost of the additives needed for emulsion polymerization excessively increases the cost of the process since it may be necessary to remove the additive in a subsequent process. Finally, the use of additives while facilitating the chemistry, may alter the resulting product in some deleterious way. For example, surfactants can act as placticizers to a polymer altering the polymer""s physical properties.
Accordingly, a preferred embodiment of the enabling technology is presented herein in the form of a dramatization process utilizing hyaluronic acid (HA), a water soluble biopolymer. It should be noted, however, that while specifically describing HA dramatization, the invention is not limited to the interracial dramatization of HA, or any other water-soluble polymer. The interracial dramatization process defined herein is applicable to any water-soluble polymer containing carboxyl and/or hydroxyl groups, or more generally, other water-soluble polymers containing nucleophilic groups. Accordingly, the scope of the invention should be limited only by the claims appended hereto.